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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2007-3-16
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pubmed:abstractText |
Development of drug resistance is one of the major obstacles in cancer chemotherapy. The molecular mechanism leading to drug resistance is still not fully understood. A10A cells, a doxorubicin-resistant subline of human squamous cell carcinoma A431 cells, showed cross-resistance to methotrexate and also resistance to the drug-induced apoptosis. The cells also showed overexpression of a mutated form of p53, p53-R273H (Arg to His at codon 273), and down-regulation of procaspase-3. Knockdown of p53-R273H by p53 small interfering RNA in A431 cells increased procaspase-3 level and sensitized the cells to drug-induced apoptosis. On the other hand, transfection of p53-R273H into p53 null human osteosarcoma Saos-2 cells down-regulated procaspase-3 level and induced resistance to the drug toxicity and drug-induced apoptosis. The results support the idea that p53-R273H may gain new functions in induction of drug resistance and impairment in drug-induced apoptosis through down-regulation of procaspase-3 level. The study sheds new light on the understanding of the gain of function and drug resistance mechanisms associated with mutant p53.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1535-7163
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
6
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1054-61
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pubmed:meshHeading |
pubmed-meshheading:17363498-Antibiotics, Antineoplastic,
pubmed-meshheading:17363498-Antimetabolites, Antineoplastic,
pubmed-meshheading:17363498-Apoptosis,
pubmed-meshheading:17363498-Bone Neoplasms,
pubmed-meshheading:17363498-Carcinoma, Squamous Cell,
pubmed-meshheading:17363498-Caspase 3,
pubmed-meshheading:17363498-Down-Regulation,
pubmed-meshheading:17363498-Doxorubicin,
pubmed-meshheading:17363498-Drug Resistance, Neoplasm,
pubmed-meshheading:17363498-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:17363498-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:17363498-Humans,
pubmed-meshheading:17363498-Methotrexate,
pubmed-meshheading:17363498-Mutation,
pubmed-meshheading:17363498-Osteosarcoma,
pubmed-meshheading:17363498-RNA, Small Interfering,
pubmed-meshheading:17363498-Transfection,
pubmed-meshheading:17363498-Tumor Cells, Cultured,
pubmed-meshheading:17363498-Tumor Suppressor Protein p53
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pubmed:year |
2007
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pubmed:articleTitle |
p53-R273H gains new function in induction of drug resistance through down-regulation of procaspase-3.
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pubmed:affiliation |
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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